Clobetasol Propionate

Tokyo, Japan and Cambridge, UK, 14 February 2025 – Nxera Pharma Co., Ltd. (“Nxera” or “the Company”; TSE 4565) provides an update on operational activities and reports its consolidated results for the fourth quarter and 12 months ended 31 December 2024. The full report can be viewed here. Chris Cargill, President & CEO of Nxera, commented: “2024 was a transformational year for Nxera during which we made excellent progress under our new company name and brand towards becoming a leading technology driven biopharmaceutical company bringing new medicines to patients in Japan and globally. “We made fantastic commercial progress, with two products – PIVLAZ™ and QUVIVIQ™ (partnered with Shionogi) – recently launched in Japan driving top line revenue growth. We plan to make these products available to patients in South Korea shortly, in addition to other key APAC markets (ex-China). “Furthermore, and importantly, we saw significant advances across our partnered pipeline in 2024, with multiple programs moving towards late-stage clinical development and generating approximately US$90 million in upfront and milestone payments. These programs address some of the fastest growing therapeutic areas of unmet need, including neurology/neuropsychiatry, metabolic diseases and immunology and inflammation. The progress made by partner Neurocrine to advance its muscarinic agonist portfolio during the year has been particularly exciting and will lead to the first Nxera-designed molecule entering Phase 3 trials in 2025. “Our three wholly owned programs are also advancing as planned in early clinical development, with several important milestones expected over the next 12-18 months. Further, the continued investment in our NxWave™ platform, alongside our collaborations with cutting-edge technology companies, is generating exciting new discovery opportunities within the GPCR target universe, and potentially beyond to other important transmembrane target classes, such as ion channels or transporters. In addition, it allows us to explore new modalities against GPCR targets of interest, such as peptides and antibodies, broadening our capabilities and opportunities even more. “Going into 2025, Nxera is well capitalized and very well positioned – with multiple clinical data readouts and other potential catalysts expected during the year – to build on the tremendous work done by our exceptional and dedicated team, as we continue our mission to bring innovative therapies to patients in Japan and around the world.” Operational Highlights for Q4 2024 Significant growth in PIVLAZ® (clazosentan sodium) 150mg sales in Japan during first full year of Nxera ownership Rapidly becoming standard of care in Japan with neurosurgeons for prevention of cerebral vasospasm in patients with aneurysmal subarachnoid haemorrhage (aSAH)Market share increased from 57% in 2023 to 69% in 2024Q4 2024 net sales of JPY 4,282 million, FY 2024 net sales of JPY 12,651 million (US$83.5 million, representing 14% growth vs FY 2023) QUVIVIQ™ (daridorexant) 25 and 50 mg launched in Japan for the treatment of adult patients with insomnia Insomnia affects about 20% of Japanese adults and is recognized as an important national issue impacting both physical and mental health.QUVIVIQ™ is a novel dual orexin receptor agonist that was successfully developed through a Phase 3 trial by Nxera Pharma Japan (“NPJ,” a wholly owned subsidiary of Nxera Pharma).QUVIVIQ™ was launched in December 2024 under a commercial partnership agreement signed in October 2024 with Shionogi, which is solely responsible for distribution and sales of QUVIVIQ™ in Japan. NPJ is responsible in part for provision of drug product. Strategy to expand market for daridorexant underway with start of Phase 3 trial in South Korea Insomnia affects an estimated 15-25% of the adult population in South Korea, or 6.5-11 million people. The randomized, double-blind, placebo-controlled Phase 3 study in adult and elderly subjects with insomnia is expected to run for 12 months with results expected during 1H 2026. Further progress in sleep/wake disorders made by partner Centessa, which initiated a Phase 2 trial of ORX750 ORX750 is an investigational, orally administered, highly potent and selective orexin receptor 2 agonist, designed using Nxera technology to target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 and other sleep-wake disorders. New multi-target partnership and licensing agreement with UK techbio company Antiverse to design antibodies for validated but challenging GPCR targets The collaboration combines Antiverse’s generative AI antibody design expertise with Nxera’s NxWave™ platform, with Nxera retaining exclusive rights to develop and commercialize any resulting candidates. Experienced Pharma Executive Makoto Sugita, M.D., Ph.D., MBA, Appointed as Chief Medical Officer and President of NPJ Dr. Sugita was formerly Vice President, Head of R&D for Bristol Myers Squibb in Japan – he brings nearly 20 years’ experience in R&D and commercial roles working within the Japanese businesses of global pharmaceutical companies. Nxera Pharma won Biotech Company of the Year and Financing Deal of the Year at the Citeline Japan Awards 2024 Awards recognize outstanding advancements and innovations in the Japanese pharma and biotech sector. Post-period Events Clinical development progress with partnered muscarinic agonist portfolio noted by Neurocrine at 43rd Annual J.P. Morgan Healthcare Conference NBI-1117568 (an oral, muscarinic M4-selective agonist) End of Phase 2 meeting with the US Food & Drug Administration completed and reiteration of plans to begin Phase 3 studies in schizophrenia in 1H 2025.Initiate Phase 2 study in bipolar mania in 2H 2025. NBI-1117570 (a dual M1 / M4 agonist) Initiate Phase 2 study in schizophrenia in 2H 2025. NBI-1117567 (an M1-preferring agonist) and NBI-1117569 (an M4-preferring agonist) Phase 1 trials underway targeting neurological and neuropsychiatric conditions with data readouts anticipated during 2025. Operational Highlights for Full Year 2024 Corporate highlights Nxera Pharma, the new name for Sosei Heptares, came into effect on 1 April 2024 along with the launch of a new corporate brand and identity designed to capture the Group’s ambition to be at the forefront of the next era of biopharmaceuticals and medicineSenior team strengthened with appointments of experienced biopharma executives Toshihiro Maeda as Chief Operating Officer and senior strategy consultant Patrick Branch as Head of Business Development for Japan and APAC Progress with in-house programs Approval of QUVIVIQ™ (daridorexant) 25 and 50 mg by the Ministry of Health, Labour and Welfare of Japan for the treatment of adult patients with insomnia received in September 2024First subject dosed in a Phase 1 trial with NXE0033744, a novel, potent, selective and gut-restricted EP4 receptor agonist in development for the treatment of Inflammatory Bowel Disease (IBD) Full ownership of NXE0027477 regained from GSK – NXE-477 is a clinic-ready, highly selective, first-in-class, oral GPR35 agonist in development as a potential new treatment for IBD. Nxera and PrecisionLife expanded their 2022 strategic R&D partnership into autoimmune disorders with the aim of identifying new drug targets and subsequently potential precision targeted therapies for complex, chronic conditions. Progress with partnered programs Approximately US$70 million in milestone payments received by Nxera based on progress made across multiple partnered programs Neurocrine presented positive Phase 2 data for schizophrenia candidate NBI-‘568 and announced its intention to advance it into Phase 3 trials in 2025, triggering a US$35 million payment to Nxera.Successful completion of long-term preclinical toxicity program with NBI-‘568, supporting its chronic dosing in future clinical trials, triggered a US$15 million payment from Neurocrine First R&D milestone reached under a multi-target discovery collaboration with AbbVie in neurological diseases resulted in a payment of US$10 million to NxeraProgress made by Centessa advancing ORX750 into and through Phase 1 development resulted in a milestone payment to Nxera of US$4.6 million US$2.5 million milestone payment received from Formosa Pharmaceuticals for US approval of APP13007 for the treatment of post-operative inflammation and pain following ocular surgery New global collaboration and exclusive option-to-license agreement signed with Boehringer Ingelheim to develop first-in-class treatments targeting all symptoms of schizophrenia Single-target agreement focused on development of novel, small molecule agonists of GPR52 discovered by Nxera with the potential to simultaneously address positive, negative and cognitive symptoms of schizophreniaNxera received EUR 25 million upfront from Boehringer Ingelheim and is eligible for an option exercise payment of EUR 60 million and further milestone payments totalling up to EUR 670 million plus tiered royalties Financial Highlights for the 12-month Period ended 31 December 2024 Revenue totalled JPY 28,835 million (US$190.4 million*), an increase of JPY 16,069 million (US$99.6 million) vs. the prior year. This increase was primarily due to the inclusion of NPJ in the scope of consolidation from July 2023 resulting in twelve months of PIVLAZ® sales being included in 2024 compared to circa five months in 2023, as well as signing one new R&D partnership agreement and the occurrence of five R&D milestone events in the current year vs. no upfront fees and the occurrence of three R&D milestone events in the prior year. R&D expenses totalled JPY 11,816 million (US$78.0 million), an increase of JPY 1,741 million (US$6.3 million) vs. the prior year. This increase primarily reflects an increased investment in R&D plus the impact of the weaker Yen. JPY 1,483 million (US$9.8 million) has been included for R&D expenses relating to NPJ/NPK.SG&A expenses totalled JPY 16,015 million (US$105.8 million), an increase of JPY 6,050 million (US$34.8 million) vs. the prior corresponding period. This increase was primarily due to an increase in SG&A expenses relating to the NPJ/NPK businesses, including an amortization charge on Idorsia related intangible assets. JPY 8,972 million (US$59.3 million) has been included for SG&A expenses relating to NPJ/NPK.Operating loss totalled JPY 5,423 million (US$35.8 million) vs. an operating loss of JPY 9,526 million (US$67.8 million) in the prior year. This improvement in profitability reflects the combined effect of all movements explained above.Loss before income tax totalled JPY 4,662 million (US$30.8 million) vs. a loss before income tax of JPY 10,680 million (US$76.0 million) in the prior year. This improvement in profitability reflects the combined effect of all movements explained above.Net loss for the year ended 31 December 2024 totalled JPY 4,838 million (US$31.9 million) vs. a net loss of JPY 7,193 million (US$51.2 million) in the prior year. This improvement in profitability reflects the combined effect of all movements explained above.Core operating profit** totalled JPY 3,606 million (US$23.8 million) vs. a core operating loss of JPY 3,076 million (US$21.9 million) in the prior corresponding period. Cash and cash equivalents as at 31 December 2024 amounted to JPY 32,268 million (US$205.8 million) having decreased by JPY 16,797 million (decreased by US$142.1 million) from the beginning of the year. *Convenience conversion to US$ at the following rates: FY 2024: 1US$ =151.43 JPY; FY 2023: 1US$ =140.53 JPY; 31 Dec 2024: 1US$ = 156.83 JPY; 31 Dec 2023: 1US$ = 141.03 JPY ** Core operating profit / loss is an alternative performance measure which adjusts for material non-cash costs and one-off costs in order to provide insights into the recurring cash generation capability of the core business. –END– About Nxera PharmaNxera Pharma is a technology powered biopharma company, in pursuit of new specialty medicines to improve the lives of patients with unmet needs in Japan and globally. In addition to several products being commercialized in Japan, we are advancing an extensive pipeline of over 30 active programs from discovery through to late clinical stage internally and in partnership with leading pharma and biotech companies. This pipeline is focused on addressing major unmet needs in some of the fastest-growing areas of medicine across neurology, GI and immunology, metabolic disorders and rare diseases, and leverages the power of our unique and industry leading GPCR-targeted structure-based drug discovery NxWaveTM platform to provide a sustainable source of best- or first-in-class candidates. Nxera employs over 350 talented people at key locations in Tokyo and Osaka (Japan), London and Cambridge (UK), Basel (Switzerland) and Seoul (South Korea) and is listed on the Tokyo Stock Exchange (ticker: 4565). For more information, please visit www.nxera.life LinkedIn: @NxeraPharma | X: @NxeraPharma | YouTube: @NxeraPharma Enquiries: Nxera – Media and Investor RelationsKentaro Tahara, VP Investor Relations and Corporate StrategyShinichiro Nishishita, VP Investor Relations, Head of Regulatory DisclosuresMaya Bennison, Communications Manager+81 (0)3 5210 3399 | +44 (0)1223 949390 | IR@Nxera.life MEDiSTRAVA (for International Media)Mark Swallow, Frazer Hall, Erica Hollingsworth+44 (0)203 928 6900 | Nxera@medistrava.com Forward-looking statementsThis press release contains forward-looking statements, including statements about the discovery, development, and commercialization of products. Various risks may cause Nxera Pharma Group’s actual results to differ materially from those expressed or implied by the forward looking statements, including: adverse results in clinical development programs; failure to obtain patent protection for inventions; commercial limitations imposed by patents owned or controlled by third parties; dependence upon strategic alliance partners to develop and commercialize products and services; difficulties or delays in obtaining regulatory approvals to market products and services resulting from development efforts; the requirement for substantial funding to conduct research and development and to expand commercialization activities; and product initiatives by competitors. As a result of these factors, prospective investors are cautioned not to rely on any forward-looking statements. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Attachment FY24YE Tanshin_NxeraPharma

QUEBEC CITY--( BUSINESS WIRE )--Devonian Health Group Inc. (“ Devonian ” or the “ Corporation ”) ( TSXV: GSD; OTCQB: DVHGF ), a clinical stage corporation focused on developing unique solutions to inflammatory diseases, today announced the results of its in vitro comparative study, which demonstrate the anti-inflammatory effect of Thykamine™, with superior potency on the inflammatory biomarkers as compared to currently marketed anti-inflammatory agents, which included various corticosteroids and a phosphodiesterase inhibitor. The assays were conducted at Department of Microbiology, Infectious Diseases, and Immunology in the Faculty of Medicine at Université Laval (Quebec City) under the leadership of Pr Louis Flamand, PhD, MBA (1) in collaboration with Dr John Sampalis, PhD, Epidemiologist, Medicine Faculty, McGill University and Dr Charles Lynde, MD from Lynde Dermatology and Associate Professor in the Department of Medicine at the University of Toronto. The primary objective of the study was to compare the anti-inflammatory potency of Thykamine™ to other anti-inflammatory agents in the market, specifically betamethasone valerate, clobetasol, crisaborole, 21-acetate hydrocortisone, pimecrolimus and prednisone. The experiment involved treating lipopolysaccharide (LPS) stimulated U937 monocytic cells with each agent. Anti-inflammatory potency was assessed by the percent inhibition of the activity of four cytokines induced by each agent. The four cytokines tested were MCP-1, MIP-1α, MIP-1β and RANTES that have been implicated in several autoimmune diseases. Percent inhibition was calculated as the reduction in lipopolysaccharide (LPS) induced cytokine activity after addition of the agent. Given that the aim of anti-inflammatory drugs is to dampen cytokine induced inflammation, these results can be used as inference to overall anti-inflammatory efficacy. All agents were tested at four increasing concentrations except for pimecrolimus that was tested at three concentrations. All culture conditions were run in hexaplicate (n=6). Cell-free supernatants were collected and immediately assayed for cytokine concentration using Pro-Carta 6 plex (Life Technologies). U937 secreted amounts of IL-6 or IL-10 that were below the detection limits of the assay and were not included in the analyses. When compared to the other agents, Thykamine™ showed clinically important and statistically significant higher inhibition potency for MCP-1 (by 28% to 136%; P< 0.009), MIP-Alpha (by 30% to 108%; P < 0.001), MIP-1 Beta (by 39% to 111%; P < 0.001). For RANTES higher inhibition was observed for all agents (by 47% to 258%) except for Crisaborole and Prednisone. In this assay, pimecrolimus did not inhibit any of the cytokine tested. “ These results support the wide spectrum anti-inflammatory properties of Thykamine™ with potency that is superior to currently marketed anti-inflammatory agents. This study indicates a multi mode of action of Thykamine™ affecting several cytokines and other biomarkers, supporting the clinical efficacy demonstrated in phase 2 studies in ulcerative colitis and atopic dermatitis in adults,” said Dr Louis Flamand, lead study investigator. “ The high potency and previously established clinical efficacy of Thykamine™ , combined with its placebo-like safety, should compel practitioners to consider its use as a first line treatment, especially with the potential safety concerns of the present standard of care,” said Dr Lynde, who was consulted on the current study and was the lead investigator in Devonian’s phase 2 study in adults with mild-to-moderate atopic dermatitis. The study’s co-investigator Dr. John Sampalis, Clinical Epidemiologist, and Professor of Medicine at McGill with extensive experience in the evaluation of treatments for autoimmune disorders commented: “ The results of this in vitro study are extremely encouraging. The favorable safety profile of Thykamine™ as demonstrated in human clinical studies and its high anti-inflammatory potency proven in this study, would position Thykamine™ as a possible first line treatment of choice for several autoimmune conditions in the early stages of the disease. This can result in steroid sparing effect and reduced need for aggressive treatments with biologics and other immune modulators, that are associated with serious side effects and long term negative consequences.” Investigators of this study are planning to submit the results in a peer-reviewed journal. (1) Pr. Louis Flamand is a director on the board of directors of the Corporation About Thykamine™ Thykamine™, the first pharmaceutical product issued from Devonian’s SUPREX™ platform, is a highly innovative product for the prevention and treatment of health conditions related to inflammation and oxidative stress including ulcerative colitis, atopic dermatitis, psoriasis, rheumatoid arthritis, and other autoimmune disorders. The anti-inflammatory, anti-oxidative and immunomodulatory properties of Thykamine™ have been demonstrated by a considerable number of in vitro and in vivo studies as well as in a Phase IIa clinical study in patients with mild-to-moderate distal ulcerative colitis and in a large phase II study in adult patients with mild-to-moderate Atopic Dermatitis. Both Thykamine™ and SUPREX™ platform are protected by several patents in North America, Europe and Asia. About Devonian Devonian Health Group Inc. is a clinical stage pharmaceutical company specializing in the development of drugs for various auto-immune inflammatory conditions with novel therapeutic approaches to targeting unmet medical needs. Devonian’s core strategy is to develop prescription drugs for the treatment of inflammatory autoimmune diseases including but not limited to ulcerative colitis and atopic dermatitis. Based on a foundation of over 15 years of research, Devonian’s focus is further supported by a U.S. Food and Drug Administration set of regulatory guidelines favoring a more efficient drug development pathway for prescription botanical drug products over those of traditional prescription medicines. Devonian is also involved in the development of high-value cosmeceutical products leveraging the same proprietary approach employed with their pharmaceutical offerings. Devonian also owns a commercialization subsidiary, Altius Healthcare Inc., focused on selling prescription pharmaceutical products in Canada, under license from brand name pharmaceutical companies. Devonian Health Group Inc. was incorporated in 2015 and is headquartered in Québec, Canada where it owns a state-of-the art extraction facility with full traceability ‘from the seed to the pill’. Devonian is traded publicly on the TSX Venture Exchange (the “Exchange”) (TSXV: GSD) and on OTCQB exchange (OTCQB: DVHGF). For more information, visit www.groupedevonian.com Cautionary Note Regarding Forward-Looking Statements All statements, other than statements of historical fact, contained in this press release including but, not limited to those relating to the economical impact of clinical study, the efficiency of the high anti-inflammatory potency proven and the position of the Thykamine™ as a possible first line treatment of choice for several autoimmune conditions in the early stages of the disease and the reduced need for aggressive treatments with biologics and other immune modulators, that are associated with serious side effects and long term negative consequences, and, generally, the above “About Devonian” and “About Altius” paragraphs, which essentially describes the Corporation’s outlook, constitute “forward-looking information” or “forward-looking statements” within the meaning of certain securities laws, and are based on expectations, estimates and projections as of the time of this press release. Forward-looking statements are necessarily based upon a number of estimates and assumptions that, while considered reasonable by the Corporation as of the time of such statements, are inherently subject to significant business, economic and competitive uncertainties and contingencies. These estimates and assumptions may prove to be incorrect. Many of these uncertainties and contingencies can directly or indirectly affect, and could cause, actual results to differ materially from those expressed or implied in any forward-looking statements. There can be no assurance that these assumptions will prove to be correct and there can be no assurance that forward-looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. By their very nature, forward-looking statements involve inherent risks and uncertainties, both general and specific, and risks exist that estimates, forecasts, projections and other forward-looking statements will not be achieved or that assumptions do not reflect future experience. Forward-looking statements are provided for the purpose of providing information about management’s expectations and plans relating to the future. Readers are cautioned not to place undue reliance on these forward-looking statements as a number of important risk factors and future events could cause the actual outcomes to differ materially from the beliefs, plans, objectives, expectations, anticipations, estimates, assumptions and intentions expressed in such forward-looking statements. All of the forward-looking statements made in this press release are qualified by these cautionary statements and those made in our other filings with the applicable securities regulators of Canada. The Corporation disclaims any intention or obligation to update or revise any forward-looking statements or to explain any material difference between subsequent actual events and such forward-looking statements, except to the extent required by applicable law. Neither the Exchange nor its Regulation Services Provider (as that term is defined in policies of the Exchange) accepts responsibility for the adequacy or accuracy of this release.